Colorectal cancer liver metastasis: genomic evolution and crosstalk with the liver microenvironment

Colorectal cancer (CRC) patients frequently develop liver metastases, which are the major cause of cancer-related mortality. The molecular basis and management of colorectal liver metastases (CRLMs) remain a challenging clinical issue. Recent genomic evidence has demonstrated the liver tropism of CRC and the presence of a stricter evolutionary bottleneck in the liver as a target organ compared to lymph nodes. This bottleneck challenging CRC cells in the liver is organ-specific and requires adaptation not only at the genetic level, but also at the phenotypic level to crosstalk with the hepatic microenvironment. Here, we highlight the emerging evidence on the clonal evolution of CRLM and review recent insights into the molecular mechanisms orchestrating the bidirectional interactions between metastatic CRC cells and the unique liver microenvironment.

Automated summary

Colorectal cancer (CRC) patients often suffer from liver metastases, resulting in high mortality rates. The molecular basis and management of colorectal liver metastases (CRLMs) pose significant challenges in the clinic. Recent genomic evidence has revealed liver tropism in CRC and a stricter evolutionary bottleneck in the liver compared to lymph nodes. This organ-specific bottleneck challenges CRC cells and necessitates adaptation at both the genetic and phenotypic levels to interact with the hepatic microenvironment. Here, we review emerging evidence on the clonal evolution of CRLM and discuss recent insights into the molecular mechanisms behind the bidirectional interactions between metastatic CRC cells and the unique liver microenvironment.